Ibuprofen Sodium: A case for pharmaceutical compounding

2-(4-Isobutylphenyl)propionic acid, known in common pharmaceutical parlance as Ibuprofen, was invented in 1968 by the two English chemists John Stuart Nicholson and Stewart Sanders Adams. It was a member of a homologous series of p-substituted phenylalkanoic acid derivatives which they synthesized, tested and confirmed to possess the pharmacologic triad of anti-inflammatory, analgesic and antipyretic effects. They have been driven in their search, per their own claims, by motives to find therapeutically useful alternatives having all the abovementioned medicinal effects and supplemented with the following advantages over Aspirin which was then the mainstay for treating rheumatic diseases, namely;

               1. Are less toxic

               2. Have higher therapeutic ratio

               3. Are more stable in the presence of water and water vapour

               4.Are more soluble in water


 The collective clinical experience with Ibuprofen up to the current time vindicates the inventors so far as higher therapeutic ratio is concerned, given that the safe daily adult dose of Ibuprofen is in the range of 600mg—3200mg (Martindale 36, 2009; pp. 64—66), but the other three purported advantages are not beyond reasonable doubts. Notwithstanding the foregoing observation, however, Ibuprofen has attained sufficient popularity with clinicians globally, and in the Ghanaian healthcare sector currently, it is the main alternative drug to Paracetamol in their category for children.

 Building on the concluding remarks of the above paragraph, it is obvious that paediatric preparations of Ibuprofen are essential pharmaceutical commodity in our local health sector. But I am not oblivious of the many different brands of Ibuprofen Suspension sitting on the shelfs of our pharmacies; when it is paediatric Ibuprofen formulation that you want in Ghana, invariably, you are served Ibuprofen Suspension. I intend to pose a puzzle here, a query that none other but a pharmacist is qualified to answer by reason of his/her chosen profession: What (at all) does it take to prepare something in the nature of Ibuprofen Oral Solution?. Think about a homogeneous liquid of Ibuprofen Oral Solution and contrast its pharmaceutical properties with those of a heterogeneous Ibuprofen Suspension. The merits of the former preparation over the latter are indisputable, including; aesthetic elegance, user-friendliness, ease of measuring dose, and accuracy of measured dose.

 That said, one should ask just what are the odds against the preparation of an Ibuprofen Oral Solution?. To the extent that my studies have revealed, it is none other hurdle than the poor solubility of Ibuprofen in water. The physicochemical characteristics of Ibuprofen are; colourless, crystalline stable solid, m.p. 75—77°C, relatively insoluble in water (Merck Index 14; p. 4886). In our conventional terminology “relatively insoluble” translates into the reality that 1000mL or more of water is required to completely dissolve just 100mg of Ibuprofen, with implication that it is practically not feasible to prepare an Ibuprofen Oral Solution at a strength of 100mg per 5mL. Hence the general tendency for the pharmaceutical industry to go the easier way; Ibuprofen Suspension 100mg/5mL.

 Pharmacy is both an art and a science, and the highly-coveted practice of the apothecaries predated the rise of the pharmaceutical industry. Amidst the rapid growth of the latter we are not to relinquish and forsake the traditional roles of our forebears the apothecaries, nor are we to succumb to pressures and be pushed out of our traditional domain. Expansion of our professional territories is desirable, but we should ever be awake to the fact that the pharmaceutical industry is our competitor, not ally. There is an Akan proverb which goes like; “A mighty warrior is worthy of his name only on the battlefront”. As pharmacists we give much meaning to our profession when we are able to bring science and art to bear to masterfully solve puzzles such as the one under consideration here. Within a spirit of competition with the pharmaceutical industry, we should aim to summon our expertise on the microscale to formulate products having added advantages for our clients.

 Now let us revert to the Ibuprofen puzzle. The compound is actually a weak acid and, as such, theoretically should be able to dissolve in an aqueous solution of a weak alkali. The dissolution of Ibuprofen powder in aqueous solution of sodium bicarbonate (NaHCO3) will convert it to Ibuprofen Sodium, which is very soluble in water, with the production of water and carbon dioxide bubbles as byproducts. Compare below the structures of Ibuprofen and Diclofenac on one hand, and Ibuprofen Sodium and Diclofenac Sodium on the other hand. It is noteworthy to state that it is Diclofenac Sodium as a soluble salt, and not the Diclofenac base, that is the form predominantly used in the formulation of almost all the Diclofenac preparations on the market. So, is it that no one has thought about Ibuprofen Sodium then?

 By stoichiometric analysis I arrived at the following formula for preparation of Ibuprofen Solution of concentration 100mg per 5mL;

                     Ibuprofen ———————— 20.00g

                     Sodium bicarbonate ———-- 8.15g

                     Purified Water to ————— 1000mL


 Method: Form alkaline solution by dissolving the sodium bicarbonate in about 2-5th (400mL) of the total volume; add the Ibuprofen powder and stir gently to completely dissolve; add sufficient amount of Purified Water to make up to total volume.

This basic formula can be adapted by including the appropriate excipients to prepare on the microscale Ibuprofen Oral Solution 100mg/5mL either by using raw Ibuprofen powder or equivalent number of preformulated Ibuprofen tablets. In the latter case, crush the Ibuprofen tablets in a mortar and comminute to produce a fine powder. Stir powdered tablet in the alkaline solution as above to extract Ibuprofen Sodium. Filter through a standard filter paper and then incorporate filtrate into the formulation.

 To conclude, I wish to affirm that pharmaceutical compounding is still a relevant role of the practising pharmacist as it was in the days of the apothecaries. Many are the pharmaceutical needs which the pharmaceutical industry has currently not filled, nor will ever be able to satisfy. We live in an era when the popular ideology is to customize or individualize healthcare interventions, that is, most of the clients we deal with will require special or unique pharmaceutical products and services. Do we as pharmacists throw up our hands in the air and look on helplessly when the pharmaceutical preparations our clients need are not available in the marketplace?. I advocate that inasmuch as we seek to expand our professional boundaries to include much of the clinical dimension we also do not forget the origins of our profession, but jealously preserve the art of the apothecaries. We need to orient our mindset to see the pharmaceutical industry as a real threat to our noble profession, not yielding to the former as helpless consumers, but formidably competing with the established industry as jealous and rightful custodians of the art and science of pharmacy. This we can do on the microscale. Every standard pharmacy, community or institutional, should necessarily be equipped with well-kept facility for purposes of pharmaceutical compounding. Let us rise above the retail-only pharmacies.